The program has a number of facets. 1. Ionic Exchange - Ionic Control of Myocardial Contractility. This component focuses upon the role of ions in regulation of the myocardial contractile response. Ionic kinetics, tissue culture and ultrastructural methodologies are used. 2. Ionic Exchange - Arrhythmias and Hypoxia. Using the perfused interventricular septum to correlate functional and ionic exchange responses with ischemia and hypoxia. Study concentrates on the definition of ionic exchange in clinical relevant conditions. 3. Mechanics of Cardiac Muscle. Directed toward the definition of the appropriate mechanical model of cardiac muscle. Techniques involve sophisticated control and analysis of mechanical perturbations in mammalian myocardium. 4. Muscle Protein Structure and Function. Biochemical methodology is used to study high energy metabolites, determination of protein structure, sarcotubular function and mechanisms for modifying gene expression in synthesis of muscle protein. 5. Electrophysiology of Cardiac Muscle Study uses cells in tissue culture to define cell to cell transmission. A system for single electrode (shared current-voltage monitoring) voltage clamping is nearing completion and will be applied to single cells. 6. Energetics. Use of sophisticated thermopile techniques to study energetics of skeletal and cardiac muscle. Heat measurements are closely correlated with biochemical measurements in order to define energy utilization in contractile tissue. 7. Coronary Blood Flow. Particular emphasis on distribution of coronary flow in the heart and its relation to function. Study emphasizes the development of subendocardial ischemia and defines the hemodynamic results.